When normal humans or dogs exercise in progressive manner, the O2 consumption of the body rises approximately linearly with the work rate. The blood lactic acid level rises slowly to 50-60 percent of the maximal metabolic rate; thereafter, it rises much more rapidly. The metabolic rate at which the lactic acid in the blood beings to increase rapidly is called the anaerobic treshold. The metabolic rate at which the anaerobic threshold occurs in patients with severe cardiovascular or respiratory disease may be reduced to levels only slightly above the resting metabolic rate. It is generally believed that the anaerobic treshold occurs when the O2 supplied to the working mussles by the blood becomes inadequate to meet the metabolic needs of the muscle. The muscle supplement their metabolism anaerobically by breaking down glycogen to lactic acid. However, the results of several studies invetigating the role of O2 transport limitation in muscle, have shown that under normoxic conditions, O2 transport to muscle does not limit the metabolic rate of muscle. Why then does the blood lactic acid level rise rapidly during high intensity exercise? The goal of this project is to discover the factors that induce muscle to produce lactic acid. The specific aims are to measure the O2, CO2, and lactic acid exchange by a single in situ mammalian skeletal muscle which would not be subjected to the hormonal, metabolite and other changes that occur in whole body exercise. Two kinds of contractions will be used, maximal steady-level repetitive tetanic contractions and progressively intense tetanic contractions. The next step will be to study acidosis, alkalosis and catecholamine infusions to discover the effects of these alterations of muscle O2, CO2 and lactic exchange during the muscle contractions. These studies will reveal the physiological conditions which determine muscle lactic acid production. The results will contribute to an understanding of the origin of anaerobic treshold, the reasons for is occurence at low metabolic rate in cardiovascular and respiratory diseases, and the causes of lactacidosis under other conditions suchas trauma and hypermetabolic states.